Dr. Olson and his colleagues will carry out a series of studies on transplantation of chromaffin cells into rat animal models of Parkinsons disease and into human suffering from this illness. In experiments involving chromaffin cell rat allografts and human xenografts, transplanted to basal ganglia targets in rats, a number of parameters will be examined - (1) donor age, (2) type of transplantation technique used, (3) host animal immune status and endocrine state, and (4) influence of chronic dopamine agonist exposure. A major emphasis will be placed on attempts to augment survival and neurite outgrowth from chromaffin cell grafts to rats by use of trophic factors. Experimental approaches to this problem will include: (1) cografting chromaffin cells with peripheral nerve minces, (2) exposure of chromaffin cell grafts to nerve growth factor and fibroblast growth factor via immersion and perfusion techniques both before and after transplantation, and (3) genetically modifying various established cells lines and primary cell cultures to synthesize and secrete nerve growth factor and fibroblast growth factor. Such genetically modified cells would be subsequently cografted with chromaffin cells, or with fetal CNS neurons in subproject 24. In addition, subtraction hybridization will be utilized to identify hitherto unknown trophic factors for dopamine neurons. Autologous chromaffin cell grafts will also be carried out in patients suffering from Parkinsons disease. In order to improve the poor long-term efficacy of such grafts reported by ourselves and others, grafts will be exposed to nerve growth factor before and after transplantation. As the work on genetic modification of cell lines proceeds, co-transplantation of those cells and chromaffin cells may be possible in man after appropriate studies of safety and efficacy.